{Reference Type}: Journal Article
{Title}: SARS-CoV-2 mutant spectra as variant of concern nurseries: endless variation?
{Author}: Martínez-González B;Soria ME;Mínguez P;Lorenzo-Redondo R;Salar-Vidal L;López-García A;Esteban-Muñoz M;Durán-Pastor A;Somovilla P;García-Crespo C;de Ávila AI;Gómez J;Esteban J;Fernández-Roblas R;Gadea I;Domingo E;Perales C;
{Journal}: Front Microbiol
{Volume}: 15
{Issue}: 0
{Year}: 2024
{Factor}: 6.064
{DOI}: 10.3389/fmicb.2024.1358258
{Abstract}: <B>UNASSIGNED: </B>SARS-CoV-2 isolates of a given clade may contain low frequency genomes that encode amino acids or deletions which are typical of a different clade.<BR><B>UNASSIGNED: </B>Here we use high resolution ultra-deep sequencing to analyze SARS-CoV-2 mutant spectra.<BR><B>UNASSIGNED: </B>In 6 out of 11 SARS-CoV-2 isolates from COVID-19 patients, the mutant spectrum of the spike (S)-coding region included two or more amino acids or deletions, that correspond to discordant viral clades. A similar observation is reported for laboratory populations of SARS-CoV-2 USA-WA1/2020, following a cell culture infection in the presence of remdesivir, ribavirin or their combinations. Moreover, some of the clade-discordant genome residues are found in the same haplotype within an amplicon.<BR><B>UNASSIGNED: </B>We evaluate possible interpretations of these findings, and reviewed precedents for rapid selection of genomes with multiple mutations in RNA viruses. These considerations suggest that intra-host evolution may be sufficient to generate minority sequences which are closely related to sequences typical of other clades. The results provide a model for the origin of variants of concern during epidemic spread─in particular Omicron lineages─that does not require prolonged infection, involvement of immunocompromised individuals, or participation of intermediate, non-human hosts.